Clinical and Experimental Hepatology最新文献

Aim of the study: We investigated whether nicotinamide adenine dinucleotide kinase (NADK) expression is selectively diminished in alcohol-associated liver cirrhosis (AC), and evaluated its potential as a biomarker for this condition.

Material and methods: Human liver samples were obtained during liver transplantation or resection procedures at Kosin University Gospel Hospital and classified into two groups: AC and non-AC (NAC). NAD⁺ and NADP⁺ levels were measured using liquid chromatography-mass spectrometry (LC-MS). RNA-seq data from the NCBI Gene Expression Omnibus were utilized to identify AC-specific differentially expressed genes (DEGs). Multi-level expression analyses and immunohistochemistry were performed to assess NADK expression in liver tissues.

Results: LC-MS analysis indicated a significant reduction in NAD⁺ and NADP⁺ levels in AC patients compared to both normal and NAC groups, with a corresponding increase in the NAD⁺/NADP⁺ ratio (AC = 3.93, NAC = 2.75, normal = 2.64). We identified 881 AC-specific DEGs, including 27 kinase-encoding genes. Multi-level expression analyses confirmed a significant decrease in NADK gene expression in AC patients. Immunohistochemistry showed a marked reduction in NADK protein expression in AC patients, underscoring its involvement in altered metabolic processes.

Conclusions: This study revealed a distinct decrease in NADK expression in AC, suggesting its utility as a molecular marker for diagnosing and understanding metabolic dysregulation in these patients. These findings provide a foundation for developing targeted therapeutic strategies for alcohol-associated liver cirrhosis.

Introduction: Type 2 diabetes mellitus (T2DM) is closely related to hepatocellular carcinoma (HCC). The pathophysiological mechanism of coexistence of T2DM and HCC is unclear. The study aimed to investigate the core genes and pathways involved in the development and progression of T2DM and HCC.

Material and methods: Datasets for T2DM and HCC were downloaded from the GEO to screen differentially expressed genes (DEGs). Protein-protein interaction (PPI) network analysis was performed on these DEGs to explore their functions and verify hub genes. These genes were validated by quantitative real-time polymerase chain reaction (qRT-PCR) and UALCAN analysis based on The Cancer Genome Atlas (TCGA). Finally, the transcription factor (TF)-miRNA-target gene network was constructed with hub genes, and visualized using Cytoscape software 3.6.1.

Results: A total of 77 common DEGs were identified. KEGG enrichment revealed that pathways of metabolic processes are enriched in T2DM and HCC. Combining the results of MCODE and CytoHubba showed that AASS, SDS, HAL, KYNU and TDO2 were hub genes. Then, we verified the above results by UALCAN analysis and qRT-PCR. Compared with normal liver tissues, the expression levels of 5 hub genes based on tumor grade were lower in liver hepatocellular carcinoma (LIHC) tissues. mRNA levels of these genes were significantly down-regulated in HepG2 and SNU-449 compared with LO2 cells. Furthermore, we depicted the TF-miRNA-gene interaction network.

Conclusions: This study proposed a strategy for exploring pathogenic mechanisms of T2DM and HCC. Network hub genes hold promise as disease status biomarkers and treatment targets for alleviating both T2DM and HCC.

About 30 years have passed since elastography was first used, with the greatest popularity in the last 10 years. The use of this diagnostic method is particularly important in patients with liver disease. FibroScan shows higher sensitivity in assessing the degree of organ steatosis and fibrosis compared to ultrasound. The noninvasive nature and ease of performance make it possible to perform the test in most pediatric patients. Owing to the correlation of the results with the histopathological evaluation, elastography replaces liver biopsy in many cases. Given the epidemic of childhood obesity observed in recent years, FibroScan testing appears to be increasingly necessary.

Aim of the study: Non-diagnostic ultrasound (US) of the gallbladder may be due to various factors. We aimed to evaluate the diagnostic performance of deep learning-based classification of gallbladder lesions on US images in patients with non-diagnostic US secondary to gallbladder factors.

Material and methods: Consecutive patients with non-diagnostic US due to calculi within the gallbladder lumen, obscuring the detailed evaluation, were identified by a research fellow from a prospective database of patients with gallbladder lesions. The US reports and images were evaluated by a radiologist blinded to the final diagnosis. Patients who had the final pathological diagnosis based on fine-needle aspiration cytology, percutaneous or endoscopic biopsy, or surgical histopathology were included. Convolution neural networks (ResNet50, GBCNet), transformer models (vision transformer [ViT], RadFormer), and a hybrid model (MedViT) were trained on a public gallbladder dataset (GBCU dataset). The performance of these models for classifying gallbladder lesions into benign and malignant was tested on non-diagnostic (GB-RADS 0) US images.

Results: Training and validation cohorts (GBCU dataset) comprised 1004 and 251 images, respectively. The testing data (26 patients, mean age [SD]: 57.5 ±8.07 years, 17 female) comprised 304 images. The best performance for detection of GBC was achieved with GBCNet (sensitivity 51.1%, specificity 83.3%, area under the curve [AUC] 0.709) and MedViT (sensitivity 92.8%, specificity 50%, AUC 0.714). MedViT had the best accuracy (73.1%) for detecting benign gallbladder lesions.

Conclusions: These results suggest that deep learning models can potentially stratify patients with non-diagnostic US. However, further improvement in the performance is needed to render this approach relevant in clinical practice.

Aim of the study: To evaluate serum concentrations of dihomo-γ-linolenic acid and associated long chain n-6 polyunsaturated fatty acids (linoleic (LA), arachidonic acid (AA)) together with estimated desaturase activities in obese children with metabolic dysfunction-associated steatotic liver disease (MASLD).

Material and methods: The prospective study included 57 children with obesity. MASLD was diagnosed according to the latest consensus. The total intrahepatic lipid content (TILC) was assessed by magnetic resonance proton spectroscopy (¹H-MRS). Fasting serum concentrations of LA, dihomo-γ-linolenic acid (DGLA) and AA were measured. The estimated Δ5 desaturase (D5D) activity was calculated based on the AA to DGLA ratio and the estimated Δ6 desaturase (D6D) activity based on the DGLA to LA ratio.

Results: MASLD was diagnosed in 25 children. DGLA was significantly higher in children with obesity in comparison to the reference group (n = 19, p < 0.01). The DGLA/LA ratio was significantly elevated, while the AA/DGLA ratio was significantly lower in obese subjects compared with the reference group. DGLA concentration and estimated D6D activity correlated positively with TILC. The ability of DGLA concentration to detect liver steatosis in ¹HMRS was significant (AUC = 0.72, p < 0.05).

Conclusions: Serum DGLA levels may be considered as a potential novel non-invasive biomarker for liver steatosis detection in children. The differences in the serum concentrations of DGLA, LA and AA between the groups and correlations found between their concentrations and other parameters suggest their potential role in pathogenesis and development of MASLD in children with obesity.

Aim of the study: Liver fibrosis affects progression of fatty liver. Epidemiological data about fibrosis in overweight/obese Egyptian patients undergoing bariatric surgery are limited. We aimed to assess hepatic steatosis and fibrosis in patients with metabolic associated fatty liver disease (MAFLD) before bariatric surgery via noninvasive tools and liver biopsy.

Material and methods: A cross-sectional study of overweight/obese MAFLD patients undergoing bariatric surgery in the Hepatogastroenterology Hospital was performed. For all recruited cases, the history was taken and clinical examination, laboratory testing, intra-operative laparoscopic liver biopsies and histopathological evaluation were conducted. Fibrosis-4 (FIB-4), NAFLD Fibrosis Score (NFS), and AST to platelet ratio (APRI) were calculated.

Results: The final number of patients with significant fibrosis was 85; of these, 24/85 (28.2%) met the MAFLD criteria (F2), 11/85 (12.9%) had advanced fibrosis (F3-F4), and 50/85 (58.8%) had no significant fibrosis (F0-F1). Fibrosis was significantly higher in the elderly, smokers, and those with diabetes, hypertension, or chronic hepatitis C virus (HCV) infection. Degree of fibrosis was positively correlated with body mass index (BMI), waist-hip ratio (WHR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride, cholesterol, serum uric acid, fasting blood sugar (FBS), and HbA_1c levels, and negatively with platelet level. Regression analysis indicated that smoking, elevated BMI, presence of diabetes and hypertension, decreased platelet level and elevated serum uric acid are predictors of significant fibrosis. Non-invasive models, such as FIB-4, NFS, and APRI provided greater accuracy for predicting significant fibrosis.

Conclusions: Significant fibrosis (F ≥ 2) was detected in > 1/3 of patients with MAFLD undergoing bariatric surgery. Presence of smoking, diabetes, hypertension, high WHR, elevated serum uric acid, advanced age, and low platelet level are risk factors for significant fibrosis (F ≥ 2). Noninvasive models, FIB-4, NFS, and APRI can be used to identify significant liver fibrosis in bariatric surgery patients.

According to the latest clinical guidelines, minimal hepatic encephalopathy (MHE) is diagnosed by using a single test for which the center has experience and local norms. Nowadays, several tests are available. Here we describe the most frequently used tests: Psychometric Hepatic Encephalopathy Score (PHES), Continuous Reaction Time (CRT), Inhibitory Control Test (ICT), Stroop test, Animal Naming Test (ANT), critical flicker frequency (CFF) and electroencephalography (EEG) using characteristics such as: creation specificity, neurocognitive domains, computerized vs. pencil and paper, translatability, time to perform, learning effect, affecting factors, local norms, copyright, medical equipment and need for specific training. After that we briefly address comparison of the results of different tests or test combinations. Such information may prove useful to anyone new to the field of minimal hepatic encephalopathy.

Aim of the study: This was a retrospective study which aimed to analyse two-year (October 1, 2020 to October 31, 2022) data collected by HIV Prevention Point employees during their routine work and to update hepatitis C virus (HCV) prevalence among residents of long-term assisted living facilities (LTALF) and shelters in Latvia. Key objectives included investigating risk factors associated with HCV infection and analysing demographic characteristics contributing to prevalence.

Material and methods: Retrospective analysis of the screening involved 46 LTALF and 6 shelters, randomly selected from Latvia's social service providers register where HCV rapid plasma immunochromatographic antibody tests were used, as well as demographic and risk-related questions asked to participants. Data were recorded, transferred to Google Sheets, and statistically analysed using SPSS software.

Results: Out of 2838 tests in LTALF and 349 in shelters, HCV prevalence was 4.2% and 12.0%, respectively. Risk factors such as intravenous narcotic use, incarceration, and unprotected sex were significantly associated with HCV prevalence in both populations. Males had higher prevalence rates than females, particularly in LTALF.

Conclusions: The study revealed an HCV prevalence in LTALF almost twice that of the general population and four times higher in shelters. Those denying prior incarceration or intravenous narcotic use still exhibited higher prevalence rates. Significant risk factors included intravenous narcotic use, prior incarceration and unprotected sex. The findings highlight the need for targeted interventions in these high-risk populations and emphasize the importance of tailored prevention, screening, and treatment strategies. The urgency of addressing elevated prevalence rates in LTALF and shelters is underscored, calling for immediate and targeted public health interventions.

Aim of the study: We aimed to compare the first, second and third trimester APRI (aspartate aminotransferase to platelet ratio index) scores in pregnant women with and without intrahepatic cholestasis (ICH).

Material and methods: In this study, 54 patients diagnosed with ICH and 59 healthy pregnant women admitted to a tertiary care center between 2018 and 2024 were evaluated. APRI scores were compared between the two groups for three trimesters (first, second, and third trimester). The optimal cut-off values of the APRI score for the prediction of ICH were analyzed.

Results: APRI scores were significantly higher in the ICH group in all trimesters (p = 0.028, p < 0.001, p < 0.001, respectively). The optimal cut-off value for APRI score to predict ICH in the first, second, and third trimesters was 0.06 (42.6% sensitivity, 83.1% specificity), 0.1 (57.4% sensitivity, 93.2% specificity) and 13 (77.8% sensitivity, 98.3% specificity), respectively.

Conclusions: APRI score was found to be a significant predictor of ICH throughout the entire pregnancy. APRI score seems to be a useful marker in clinical practice to predict ICH.

Aim of the study: Chronic liver disease is a global cause of morbidity and mortality. Slovakia has a high prevalence but an inadequate hepatology network. The COVID-19 pandemic catalysed telemedicine (TM) as a potential solution, which we aimed to investigate.

Material and methods: We conducted a retrospective cohort study to evaluate the feasibility and benefits of TM for liver cirrhosis and posttransplant patients, consisting of two phases, TM1 and TM2. The main outcomes were 1) cumulative endpoint of feasibility, uptake/acceptance, adherence (TM1), and fidelity (TM1, TM2), 2) the potential to reduce the length of hospital stay, avert unnecessary hospital admissions, and expedite the search/recall process in case of serious signals mediated by TM. Although not analysed in this study, we have recorded variables necessary for investigating associations of TM use with clinical outcomes and healthcare expenditure.

Results: The study included 95 patients. The adherence documented by the termination of monitoring at the designated time was higher in TM2 (81.7% vs. 58.3%). The proportion of patients terminated due to death or the physician's decision decreased (16.9% vs. 29.2%) and was based on their discretion, unrelated to any health complications (1.4% vs. 12.5%). The clinical impact was reflected in the hospitalization rate, particularly shortened hospitalization in 11.3%, averted/prevented hospital admissions in 14.1%, and accelerated rehospitalization in 11.3% in the subsequent phase with alert-based interventions.

Conclusions: This study showed that adherence to TM was high and integrating TM helps to reduce hospitalization rates. Despite the identified limitations, TM has the potential to improve the quality and substantially reduce the cost of care.